Causal association between kynurenine and depression investigated using two-sample mendelian randomization.

As research progresses, the intricate metabolic connections between depression and tryptophan, as well as kynurenine (KYN), have become increasingly evident. In studies investigating the relationship between KYN and depression, the conclusions reached thus far have been inconsistent. Therefore, we propose employing a two-sample mendelian randomization (MR) approach to further elucidate the relationship between KYN and depression. We utilized extensive data from large-scale genome-wide association studies to identify single nucleotide polymorphisms that act as instrumental variables for kynurenine and depression in European ancestry populations, ensuring compliance with MR assumptions. We employed five MR algorithms, namely, weighted median, MR-Egger, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW as the primary analysis method. Sensitivity tests were conducted using Cochran's Q test, MR-Egger intercept test, MR Pleiotropy Residual Sum and Outlier, and Leave-one-out analysis.The IVW analysis revealed that each standard deviation increase in kynurenine corresponded to a 1.4-fold increase in the risk of depression (OR = 1.351, 95% CI 1.110-1.645, P = 0.003). The direction of the effect size (positive or negative) was consistent with the findings from the other four algorithms. Sensitivity tests indicated no heterogeneity or horizontal pleiotropy among the instrumental variables. Elevated levels of kynurenine have a causal relationship with an increased risk of developing depression.

A transdiagnostic comparison of affective decision-making in patients with schizophrenia, major depressive disorder, or bipolar disorder.

Deficit in decision-making has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), respectively, while the common and distinct characteristics of this deficit among these patients are still unclear. The present study aimed to make a transdiagnostic comparison of the affective decision-making ability in patients with SCZ, MDD, and BD. In this study, 33 patients with SCZ, 23 patients with MDD, 29 patients with BD, and 34 healthy controls (HCs) were recruited and the Iowa Gambling Task (IGT) was used to assess the affective decision-making ability. The results showed that all three diagnostic groups tended to select the disadvantageous decks but not advantageous decks compared to HCs. For patients with SCZ, an excessive preference for the disadvantageous decks with larger-magnitude less frequent punishments (deck B) may be the main reason of the deficit in affective decision-making, while that in patients with MDD was a significantly decreased ability to choose advantageous decks on the whole but with larger-magnitude less frequent punishments (deck D). As regards patients with BD, the concurrence of more choices of deck B and fewer choices of deck D was the characteristic of the deficit in affective decision-making. Our findings suggest a common affective decision-making impairment in the context of multiple choices in patients with SCZ, MDD, and BD, while the underlying mechanisms of the impairment among these patients may be slightly different.

Emotion-behavior decoupling in individuals with schizophrenia, bipolar disorder, and major depressive disorder.

Failure in translating emotional salience into effortful behavior is thought to be a core feature of anhedonia and avolition in individuals with schizophrenia (SCZ), but little is known about emotion-behavior coupling in individuals with bipolar disorder (BD) and major depressive disorder (MDD). In this study, we compared emotion-behavior correspondence in participants with SCZ, BD, and MDD. Forty-two participants with SCZ, 44 participants with MDD, 43 participants with BD, and 43 healthy controls were recruited. A computerized anticipatory and consummatory pleasure task was used to evaluate emotion-behavior correspondence. Clinical ratings of negative symptoms and self-report anhedonia questionnaires were also administered. We found that participants with SCZ, MDD, and BD exhibited different levels of negative symptoms and self-reported anhedonia, as well as emotion-behavior decoupling. In SCZ participants, both desirable and undesirable images elicited lower correspondence between self-reported liking and behavior. In MDD and BD participants, undesirable images elicited lower emotion-behavior correspondence under both direct stimulus presentation and representation conditions, whereas deficits in emotion-behavior coupling under desirable conditions were only observed when stimuli were present. Taken together, emotion-behavior decoupling showed both common and unique patterns in participants with SCZ, MDD, and BD, and showed some associations with negative symptoms and anhedonia across the combined clinical sample. This finding may be helpful for early identification and the development of novel interventions for different psychiatric diagnoses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).